Table 1.

Summary of Discussed Immunotherapeutics

Drug	Clinical Trials	Pre-Clinical Animal Studies
Oxycodone	Oxy(Gly)4-sKLH Phase 1/2: Still ongoing with an estimated completion date of December 30, 2023.21	Oxy-TT %50 lower oxycodone brain concentrations in Oxy-TT rats compared to TT rats.22
Heroin		Her–KLH, Mor-KLH Effective blockade of drug activity and prevention of the drug abuse in rats.25 Heroin-HIV-1 (H2) vaccineHigh endpoint titers and attenuation in heroin induced antinociception and hyperlocomotion.27
Morphine		KLH-6-SM Production of anti-morphine antibodies and decreased behavioral effects, and a 25% decrease in brain levels of morphine in rats.28 M(Gly)4-KLH High retention of all three opioids in plasma compared to controls and lower heroin-induced locomotor activity in rats.26
Fentanyl		FEN-CRM Blockade of drug-related analgesia and decreased CNS penetration of drug in mice.31 Fentanyl-TT Up to 33-fold anti-nociceptive potency shift and significant protection from lethal fentanyl doses in mice.32 22-fold potency shift in fentanyl vs food choice, and a significantly blunted fentanyl reinforcement in rats33 Significant potency shifts in fentanyl’s behavioral effects and a substantial change of fentanyl potency to produce antinociception in rhesus monkeys.34
Nicotine	NicVax Phase 3: Ineffective in increasing abstinence.42 Phase 2: 12.5% reduction in nicotine binding to b2*-nAChRs in the brain.43 TA-NIC Phase 1: Abstinence in 38% of the vaccine group compared to 8% in the placebo group.45 Phase 2: No results published.46 Nic-Qb (NIC002) Phase 1: Production of nicotine-specific Ig G and Ig M antibodies in day 7 and 14.48 Phase2b: abstinence rates were 20.2% higher in vaccine group compared to placebo.47 SEL-068 Phase 1: No results reported.50 Niccine Phase 2: Higher nicotine antibody levels in vaccine group. However, nonsignificant difference in relapse rates between two different groups.51 NIC7-001, NIC7-003 Phase 1: No results published.53	Nic-Qb (NIC002) Higher levels of antibody and reduced nicotine levels in brain of mice.48 SEL-068 Dose dependent inducing effects on antinicotine antibodies in male squirrel monkeys.49 NIC7-001, NIC7-003 Generation of anti-nicotine antibodies in primates.52 Nic311 Lower brain levels of nicotine and reduced locomotor activity in rats.54
Cocaine	TA-CD Phase 2: Clinically significant relationship between attaining high anti-cocaine antibody levels and reduced cocaine use.54 Phase 3: Clinically unsignificant difference in abstinence rate between placebo and vaccine group.57 dAd5GNE Phase 1: still ongoing with an estimated completion date of December 202564 TV-1380 Phase2: Dose dependent increase in abstinence rates between placebo and vaccine group.63 RBP-8000 Phase 2: Up to 90% decrease in plasma concentration and in physiological effects of cocaine in intervention group.62	dAd5GNE Reduced cocaine occupancy in the brain of primates.59 Mitigation in the effects of cocaine in different organs in primates.60 TV-1380 Decrease in intoxicating effects of cocaine and drug seeking behavior in rats.66 RBP-8000 Three times faster elimination of cocaine from rhesus-monkeys brain intervention group.67 GNCgzk IgG prevention of acute toxicity and lethality of cocaine in mice.72 AAVrh.10 antiCoc.Mab sequestration of cocaine in the blood and reduced cocaine-induced behavioral effects in mice.73
Methamphetamine	Anti-METH mAb7F9 (ch-mAb7F9(IXT-m200)) Phase 1: No results published.81 Phase 1/2: Results pending.82	MH6-KLH Attenuation in drug self-administration and a positive correlation between plasma drug concentration and antibody titer in rats.77 Mitigation in drug-induced physiologic effects and lowered brain drug concentration in rats.78 SMA-TT Decreased drug levels in vaccinated mice and attenuation in drug acquisition and reinstatement.84
Cathinone		α-PVP-KLH, MDPV-KLH Decreased locomotor activity and self-administration behavior in rats.85 Decreased reinforcing effects of drug in high doses of vaccine. However, failure in Altering self-administration behavior in rats.86
Synthetic cannabinoids		Drug targeting haptens Cross reactivity for two different class of synthetic cannabinoids, decrease in locomotion and temperature in rats.94
Ketamine	NK-N-COOH, KET-N-COOH, HNK-N-COOH Antibody response against ketamine and 6-Hydroxynorketamine.97